Death Risk Higher in African Americans After 10 Years of Antiretroviral Therapy

Black men and women starting antiretroviral therapy in the United States had a 7% to 8% higher risk of death after 10 years of treatment than white men, according to results of a 10,000-person study.1 White women and Hispanic women and men had lower 10-year mortality than white men.

Antiretroviral therapy now helps many people with HIV live as long as HIV-negative people. But some research shows survival differences between antiretroviral-treated women versus men and between racial groups.2,3 Reasons for these differences may include differences in response to antiretroviral treatment, consistent pill taking, income, insurance, education, access to steady care, and other health-related behaviors like diet and exercise.

To get a new look at survival on antiretroviral therapy according to sex and race in a large U.S. group, and to explore reasons for potential differences, researchers working with the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) conducted this study.

How the Study Worked

The study involved HIV-positive adults who began antiretroviral therapy between January 1, 1998 and December 30, 2011 at one of eight U.S. HIV clinics in the CNICS study. CNICS centers regularly collect data on patient characteristics (like age and sex), CD4 count and viral load, medication use, and death. The study included only people who described themselves as black, white, or Hispanic.

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Researchers monitored study participants from the day they began antiretroviral therapy until December 31, 2011, until they had taken antiretrovirals for 10 years, or until they died. They determined who died from any cause by analyzing HIV clinic records, death certificates, and the U.S. Social Security Death Index. The main study outcome was time from starting antiretroviral therapy to death according to sex and race.

The study team used standard statistical methods to compare death risk between men and women and between blacks, whites, and Hispanics. This kind of analysis can estimate the risk of death by sex or race independently of other death risk factors, like CD4 count. The researchers also compared death rates in HIV-positive people with death rates in the U.S. general population according to age and sex.

To explore possible reasons for differences in death rate by sex and race, the researchers calculated (1) proportions of study participants who stayed in care (indicated by no gaps in lab monitoring of more than 1 year within 2 years of starting antiretrovirals) and (2) proportions of participants who reached a viral load below 400 copies in the first year of antiretroviral therapy.

What the Study Found

The study focused on 10,017 people, 1858 of them (18.5%) women (1232 black, 457 white, 169 Hispanic) and 8159 (81.5%) men (2679 black, 4228 white, 1252 Hispanic). Overall, 1758 people (18%) injected drugs and 1572 (16%) had hepatitis C virus (HCV) infection. Study participants had a median age of 40 years, and half began antiretroviral therapy in 2006 or later.

Researchers tracked study participants for a median of 4.7 years, and during that time 1224 people died from any cause. Overall, the probability of death 10 years after starting antiretroviral therapy was 20.2%. Ten-year mortality varied by race and sex (Figure 1), being highest in black men and women, lower in white men and women, and lowest in Hispanic men and women.

10-Year Risk of Death by Race and Sex in 10,000 U.S. HIV Patients

Figure 1. Risk of death 10 years after antiretroviral therapy began was substantially higher in black men and women than in white men and women, and somewhat lower in Hispanic men and women than in whites in a study of 10,000 people treated at eight U.S. clinics.

Next the researchers figured 10-year death risk in these six groups in an analysis that factored in the potential impact of several factors on death risk, including age, calendar year, CD4 count, and viral load when antiretroviral therapy began. Compared with white men, black men had a 7.2% higher 10-year death risk and black women a 7.9% higher risk. But compared with white men, white women had a 4.0% lower 10-year death risk, Hispanic women a 7.1% lower risk, and Hispanic men a 3.2% lower risk. Overall, black people had an 8.2% higher 10-year death risk than white people, and Hispanic people had a 2.7% lower 10-year death risk than white people.

The higher mortality in black men with HIV than white men with HIV was greater than that difference in the general population of U.S. men. The higher mortality in black women with HIV than white men with HIV was much greater than that difference in the general population of U.S. women and men.

One year after antiretroviral therapy began, only 59.9% of black patients had an undetectable viral load, compared with 70.9% of white patients and 72.0% of Hispanic patients. These rates did not differ much between men and women. The proportion of patients who remained in care 2 years after starting antiretroviral therapy did not differ much by race or sex.

What the Results Mean for You

This large study of HIV-positive people starting antiretroviral therapy across the United States found 10-year mortality (death rate) from any cause significantly greater in blacks than in whites but lower in Hispanics than in whites. Blacks have a higher death rate than whites in the general population of the United States. But the higher death rate in HIV-positive blacks than whites in this study exceeded differences in death rates seen in the general population.

Differences in the quality of HIV care cannot explain these differing death rates because everyone in the study was receiving care at the same eight HIV clinics, and death rates did not differ much from one clinic to the next. Also, blacks, whites, and Hispanics in this study were equally likely to remain in care 2 years after starting antiretrovirals. Other factors -- like CD4 count and viral load before antiretroviral therapy began -- cannot explain the different death rates because the researchers used a statistical method that accounted for the impact of pretreatment factors like CD4 count and viral load.

The study did turn up one clue to the higher death rate in blacks than whites: One year after antiretroviral therapy began, 71% of whites and 72% of Hispanics had an undetectable viral load, compared with only 60% of blacks. Higher viral loads certainly raise the risk of AIDS and can raise the risk of some non-AIDS diseases. So the lower undetectable rate in blacks than in whites or Hispanics may partly explain their worse 10-year mortality. Other studies found more missed clinic visits and more inconsistent antiretroviral pill taking among HIV-positive U.S. blacks than whites,4,5 and these differences could also contribute to a higher death rate among blacks in this study.

Interpreting the lower death rate in Hispanics than whites in this study is even more difficult. In the general U.S. population, the researchers note, Hispanics survive longer than whites, and the reasons for this longer survival remain poorly understood. The longer survival among HIV-positive Hispanics than whites in this study was not as great as the longer survival among Hispanics than whites in the general population. Viewed from that perspective, HIV-positive Hispanics in this study seemed to lose some of their survival advantage over whites.

The authors also point out that widely diverse groups can fit under the label "Hispanic" -- for example, people from very different countries, and people living in the United States for a few months or for many decades. For this reason, it's hard to pinpoint one or two traits among Hispanics that make their survival differ from whites.

Finally, the study found that survival of HIV-positive women versus men differed by race. Black women had shorter survival than black men, but white and Hispanic women had longer survival than white or Hispanic men. The researchers note that people of different race or sex may also differ in many other ways, including income, social status, environment, and risk of discrimination or violence. All of these factors have an impact on survival. Combined effects of these factors probably help explain the different death rates in this study between blacks, whites, and Hispanics and between men and women. But a study like this cannot sort out the diverse impacts of these many different factors.

One clear message of this study for people with HIV is that reaching and keeping an undetectable viral load after starting antiretroviral therapy are important for longer survival. And other studies produced strong evidence that keeping clinic appointments and taking antiretrovirals and other medications on time -- as directed by your HIV provider -- are also critical to living longer with HIV. Anyone who has difficulty keeping clinic appointments or taking medications on time should talk to their provider about these problems. Working together, patients and providers can pin down causes of these problems and perhaps find solutions.

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